Erick Sell

Central Nervous System Vasculitis With Positive Antithyroid Antibodies in an Adolescent Boy

Hashimotos encephalopathy is diagnosed when patients exhibit features of corticosteroid-responsive encephalopathy and positive antithyroid antibodies. The relationship between antithyroid antibodies and encephalopathy is subject to considerable debate. We describe corticosteroid-responsive encephalopathy in a 14-year-old boy with positive antimicrosomal antibodies. His history included subtle neurocognitive decline. He presented with seizures. He underwent a brain biopsy before initiating treatment after his third episode. That biopsy was consistent with central nervous system vasculitis. This report is unique because, to our knowledge, it describes the first pretreatment brain biopsy of a pediatric patient who fits the criteria for Hashimotos encephalopathy.

Matchmaking facilitates the diagnosis of an autosomal-recessive mitochondrial disease caused by biallelic mutation of the tRNA isopentenyltransferase (TRIT1) gene

Deleterious variants in the same gene present in two or more families with overlapping clinical features provide convincing evidence of a disease–gene association; this can be a challenge in the study of ultrarare diseases. To facilitate the identification of additional families, several groups have created “matching” platforms. We describe four individuals from three unrelated families “matched” by GeneMatcher and MatchMakerExchange. Individuals had microcephaly, developmental delay, epilepsy, and recessive mutations in TRIT1. A single homozygous mutation in TRIT1 associated with similar features had previously been reported in one family. The identification of these individuals provides additional evidence to support TRIT1 as the disease‐causing gene and interprets the variants as “pathogenic.” TRIT1 functions to modify mitochondrial tRNAs and is necessary for protein translation. We show that dysfunctional TRIT1 results in decreased levels of select mitochondrial proteins. Our findings confirm the TRIT1 disease association and advance the phenotypic and molecular understanding of this disorder.

Congenital microcephaly: Case definition & guidelines for data collection, analysis, and presentation of safety data after maternal immunisation

2017 Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

COL4A1 mutation in a pediatric patient presenting with post-ictal hemiparesis.

a six-year-old girl presented with a prolonged left sided paresis and acute complete right hemispheric injury of uncertain mechanism following an episode of convulsive status epilepticus. She was born at full term after an uneventful pregnancy. at day two of life, she had three consecutive seizures and magnetic resonance imaging (MRi) revealed an intraparenchymal small bleed in the right frontal lobe. Full coagulation workup was done which was negative. She was successfully treated with phenobarbital. Follow-up MRi at seven months revealed right frontal porencephaly and volume loss of the right hemispheric subcortical white matter, basal ganglia, thalami, cerebral peduncle and corpus callosum. abnormal signal in the right cerebellar hemisphere was also identified. at 12 months-of-age, brain computed tomogram angiography indicated no evidence of arteriovenous malformations. Electroencephalogram (EEG) at 18 months-of-age showed a mildly disorganized background for age and asymmetry throughout the recording with lower amplitudes in the right hemisphere. Neurological examinations were consistently abnormal with increased reflexes on the left and a tendency to favor her right side. at two years-of-age, repeat MRi with MRa was unchanged and there was no evidence of vasculopathy (Figure1a). She remained seizure-free. Pheno-barbital was discontinued and she was discharged from follow-up. the child then presented to our emergency department at six years-of-age with a generalized tonic-clonic seizure that lasted 35 minutes and was aborted with intravenous lorazepam and dilantin. Seizure onset was not witnessed, however several hours earlier she had awoken from sleep with a headache, sore throat, malaise and complaints of being warm. Physical examination after recovery from her seizure revealed normal vitals and she was afebrile. She was found to have dysarthria, a left homonymous hemianopsia, a left dense hemiparesis, and left sided upper motor neuron signs including a left extensor plantar response. blood work including cultures, extractable nuclear antigen, antinuclear antibodies, and a coagulation profile were all normal. a cardiology assessment including electrocardiogram and echocardiogram were normal. brain MRi demonstrated diffuse right cortical and subcortical edema with associated reduced diffusivity of water motion in the right hemisphere, involving areas supplied by both the anterior and posterior circulations (Figure 2). the MRa studies indicated no evidence of a vascular malformation or vessel abnormalities. Previously described structural abnormalities were unchanged. an EEG revealed abnormal background and right-sided diffusely low COL4A1 Mutation in a Pediatric Patient Presenting with Post-Ictal Hemiparesis

Valproic acid as a monotherapy in methyl-CpG-binding protein 2 gene (MECP2) duplication-related epilepsy

Duplication of the methyl-CpG-binding protein 2 gene (MECP2) is a rare condition that results in epilepsy in half of the cases. Although this condition has been well characterized in the literature, there is a lack of research on MECP2 duplication-related epilepsy and its management. We present the case of an eleven-year old male with MECP2 duplication and epilepsy, who was resistant to polytherapy. The patient responded well to valproic acid (VPA) initially and upon re-challenge. This case report provides evidence for the use of VPA as an initial monotherapy for treatment of drug-resistant MECP2 duplication-related epilepsy.

Broad spectrum of neuropsychiatric phenotypes associated with white matter disease in PTEN hamartoma tumor syndrome

White matter lesions have been described in patients with PTEN hamartoma tumor syndrome (PHTS). How these lesions correlate with the neurocognitive features associated with PTEN mutations, such as autism spectrum disorder (ASD) or developmental delay, has not been well established. We report nine patients with PTEN mutations and white matter changes on brain magnetic resonance imaging (MRI), eight of whom were referred for reasons other than developmental delay or ASD. Their clinical presentations ranged from asymptomatic macrocephaly with normal development/intellect, to obsessive compulsive disorder, and debilitating neurological disease. To our knowledge, this report constitutes the first detailed description of PTEN‐related white matter changes in adult patients and in children with normal development and intelligence. We present a detailed assessment of the neuropsychological phenotype of our patients and discuss the relationship between the wide array of neuropsychiatric features and observed white matter findings in the context of these individuals.

Neonatal encephalopathy: Case definition & guidelines for data collection, analysis, and presentation of maternal immunisation safety data

http://dx.doi.org/10.1016/j.vaccine.2017.01.045 0264-410X/ 2017 Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). ⇑ Corresponding author. E-mail address: contact@brightoncollaboration.org (E. Sell). 1 Present address: University of Washington, Seattle USA. 2 Brighton Collaboration homepage: http://www.brightoncollaboration.org. Erick Sell a,⇑, Flor M. Munoz , Aung Soe , Max Wiznitzer , Paul T. Heath , E.D. Clarke , Hans Spiegel , Daphne Sawlwin , Maja Šubelj , Ilia Tikhonov , Khorshid Mohammad , Sonali Kochhar , for The Brighton Collaboration Acute Neonatal Encephalopathy Working Group

Pointed rhythmic theta waves: a unique EEG pattern in KCNQ2-related neonatal epileptic encephalopathy

We report the case of an infant with KCNQ2-related neonatal epileptic encephalopathy presenting with intractable seizures beginning on the second day of life, which were resistant to multiple antiepileptic drugs. Continuous EEG recordings starting on the sixth day of life demonstrated a unique pattern of inter-and postictal focal rhythmic pointed theta waves of lambdoid morphology in the immediate postictal period, localizing to the side of the antecedent seizure. Interictal EEG exhibited discontinuous background, including patterns of burst suppression and multifocal discharges, predominantly in the centrotemporal regions, which were aggravated during sleep. MRI demonstrated T1 signal abnormalities in the basal ganglia, bilaterally. Genetic testing revealed a de novo missense mutation in KCNQ2 at position c.545 T>G, encoding a previously unreported substitution (p.Val182Gly). Seizure control was achieved immediately after starting a lidocaine infusion at age 4 weeks. The patient remained largely seizure-free following add-on oral carbamazepine for maintenance therapy and weaning off lidocaine. This is the first report of a patient with KCNQ2-related neonatal epileptic encephalopathy and therapy-refractory seizures aborted by lidocaine, demonstrating a unique EEG pattern of inter- and postictal focal rhythmic pointed theta waves. Whether this pattern could be an early EEG marker for this disorder remains to be confirmed. [Published with video sequences on www.epilepticdisorders.com].